Macro-creatine kinase-BB: observations on 6 patients.

From 2000 sera with elevated total creatine kinase (EC 2.7.3.2) activity the sera of 6 patient showed a persistent high and anamnestically inexplicable creatine kinase activity level. The serum isoenzyme pattern was analyzed by four different methods. Electrophoresis revealed an atypical creatine activity band located between creatine kinase-MM and creatine kinase-MB. An adequate estimation of the persistent enzyme activity could only be achieved by immunotitration (immunoprecipitation), which identified the creatine kinase activity as due primarily to the isoenzyme creatine kinase-BB. Other methods (immunoinhibition and column chromatography) may lead to misinterpretations. The atypical serum creatine kinase-BB showed a higher molecular weight (Mr = 250,000) and altered substrate affinity as compared to native creatine kinase-BB. Both properties are attributable to the binding of creatine kinase-BB to immunoglobulins.